The molecular biology of vaccinia virus infection will be studied with focus upon: (a) the enzymatic activities present in vaccinia cores which are responsible for the synthesis, post-transcriptional modification, and transport of messenger RNA from these particles; (b) the nature of the cytoplasmic vaccinia DNA0factories with particular emphasis on the nature of the proteins which hold the DNA in a partially condensed form and the possible relationship of these proteins to DNA replication and packaging of vircal DNA will be determined; (c) transcriptive control mechanisms occurring in infected cells will be further investigated with particular emphasis on the role of double-stranded RNA and polyadenylic acid sequences. The ability of a variety of viruses to reproduce in enucleated cytoplasm prepared by the use of the drug Cytochalasin B will be investigated. Similarly, the ability of the interferon system to function in cells without a nucleus will be studied. The Cytochalasin technique for enucleation of cells will be extended to develop a procedure for the transplantation of nuclei in tissue culture cells. This method, if successful, will be employed to answer a number of questions relating to the role of the cytoplasm in the state of differentiation of the nucleus and in the determination of the oncogenic state.